Comparative Study of Macular Vascular Density and Retinal Thickness in Myopia Children with Different Microscope Diopters Based on OCTA

In order to study the vascular density and retinal thickness of myopic children, a depth study was carried out on the basis of OCTA microscope. Through the methods of prospective cross-sectional research, statistical analysis, and basic data comparison, the research examination of myopia children under OCTA was successfully analyzed. There were signi ﬁ cant di ﬀ erences in the density of super ﬁ cial capillaries in the whole macular region, inner ring, temporal side of inner ring, and nasal side ( P = 0 : 033 , 0.024, 0.018, 0.032), and there was no signi ﬁ cant di ﬀ erence in other ranges ( P > 0 : 05 ). Macular fovea, as the most sensitive part of the retina, has pathological changes, which will also lead to serious negative e ﬀ ects on vision. The limitations of cross-sectional studies include the results of a relatively small sample size. After the study of OCTA in the macular region of children with myopia, it is related to the progressive atrophy of the retina and choroid in the macular region. When there are obvious pathological changes in the macular region, the thickness of the macular region becomes signi ﬁ cantly thinner. We found that there was a positive correlation between retinal vascular density and retinal thickness in the fovea and above of myopia. The retinal thickness of the whole macular region, the inner ring and its four quadrants, and the outer ring and its four quadrants were positively correlated with SE (standard error) (all P < 0 : 05 ); Foveal ring retinal thickness was not associated with SE.


Introduction
The changes of retinal vascular density and thickness in the macular region of adolescents with different degrees of myopia and their correlation were studied by optical coherence tomography and vascular OCTA imaging. Relevant reports show that ametropia has become the second general disability disease in the world, which will seriously affect the health and visual function of patients. Myopia is the highest incidence of refractive errors in the world. With the continuous changes of people's lifestyle in recent years, the incidence rate of myopia is increasing year by year, and it is beginning to become younger. Relevant data show that the number of myopia in China accounts for about 33% worldwide, which is 10% higher than the world average. It has become an important public health problem. Juvenile myopia has become a major public health problem in the world. It is estimated that 13% of children will become highly myopia by 2050. Lutein, also known as "eye gold," is the most important nutrient in the human retina. Lutein is contained in the macula (center of vision) and lens of the retina of the eye, especially in the macula. Lutein is an important antioxidant and a member of the carotenoid family, also known as "phytolutein." It coexists with zeaxanthin in nature. Scientific research has shown that lutein is the only carotenoid found in the retina and lens of the eye. This element cannot be manufactured by the human body and must be supplemented by external intake. Without this element, the eyes will be blinded. Ultraviolet and blue light from sunlight entering the eyes will produce a large number of free radicals, leading to cataracts, macular degeneration, and even cancer. Lutein can filter blue light, decompose the damage of strong light and ultraviolet rays to the human eye, so as to avoid the damage of blue light to the eye, and prevent vision deterioration and blindness caused by the lack of lutein, so lutein is also called the eye's guardian. High myopia has a high probability of vascular related fundus complications. Due to the limitations of previous detection techniques, we can rarely observe the subtle changes of fundus blood vessels in healthy adolescents with myopia. In recent years, the emerging optical coherence tomography angiography (OCTA) can obtain the blood flow and structural information of retinal vessels and choroidal microvessels in a noninvasive, high-resolution, and three-dimensional way, which provides a new method for clinical observation of fundus vessels and structures in myopia children. In patient groups with different diopters, the application of the same OCTA can show obvious differences in retinal vascular density and thickness in macular area. There is a positive correlation between density increase and thickness thickening in relevant patients. The close relationship between them can be found through relevant examination and control, as shown in Figure 1. The superficial retinal vascular density and retinal thickness in the fovea and parafovea of four groups of myopia were collected and analyzed by OCTA. Results the superficial vessel density and retinal thickness of macular fovea were not correlated with equivalent spherical lens (r = 0:119, 0.221; P > 0:05) and ocular axis length (r = −0:026, -0.119; P > 0:05). There was a positive correlation between superficial vascular density and retinal thickness (r = 0:674). The vascular density and retinal thickness of the superficial layer near the fovea were positively correlated with the equivalent spherical mirror (r = 0:429, 0.379; P < 0:05) and negatively correlated with the length of the ocular axis (r = −0:297, -0.274; P < 0:05). There was no correlation between superficial vascular density and retinal thickness (r = 0:199, P > 0:05).

Literature Review
Gus and others said whether there will be changes in retinal choroidal microvessels and blood flow with the elongation of ocular axis in the process of progressive myopia in children.
To study the application of the emerging OCTA technology to detect the retinal choroidal blood flow and structure in the macular region of myopia children [1], Xiu and others believe that theoretically, the perfusion of central retinal artery may be related to the thickness of inner retina, and the perfusion of ciliary artery may be related to the thickness of outer retina and choroid. The superficial and deep retinal vessels are located in the inner retinal tissue. There is no significant difference in the inner retinal thickness among the three groups in the study, and there is no correlation between the superficial and deep retinal vessel density and the inner retinal thickness [2]. Chan and others believe that the pathological changes of fundus macula caused by myopia are an important reason affecting visual function. Therefore, studying the changes of retinal tissue structure in patients with myopia is helpful to early detect macular lesions, so as to provide guidance for early diagnosis and clinical treatment of the disease [3]. Nambudiri and others said that the macula, as the most sensitive part of vision on the retina, plays an extremely important role in visual function. Once the macular retina has abnormal deformation, hole, or bleeding, it will seriously damage the patient's visual function and reduce the patient's quality of life [4]. Therefore, Li and others believe that due to the limitations of detection methods, it is impossible to carry out accurate morphological quantitative examination and functional measurement of myopia macular retina in clinic. With the gradual development of imaging technology, optical coherence tomography angiography (OCTA) began to be applied in clinic and achieved ideal results [5]. Rahmati and others believed that the equivalent spherical lens in the mild myopia group, moderate myopia group, high myopia group, and ultrahigh myopia group showed a gradual decreasing trend, while the axial length showed a gradual increasing trend. There were statistically significant differences in indexes between groups (all P < 0:05) [6]. Therefore, Doubi and others studied that the retinal vascular density and retinal thickness of fovea, parafovea, temporal side, upper, nasal side, and lower in the ultrahigh myopia group were significantly lower than those in the mild myopia group, moderate myopia group, and high myopia group [7]. Yamada and others said that myopia is the most common eye disease in the world. The prevalence of myopia among children in East Asia and Southeast Asia, especially Singapore, Japan, Korea, Taiwan, Hongkong, and Chinese mainland, has reached 80% to 90%. The prevalence of myopia in Sydney, Europe, the United States, and Israel is also increasing by [8]. Hashemi and others believe that at this stage, myopia will lead to degenerative changes in the retina, such as thinning of the retina, reduction of the thickness of nerve fiber layer, and atrophy around the optic disc. Retinal degenerative changes in myopia are related to the decrease of retinal blood flow and vascular changes [9]. Li believes that the increase of myopia degree and the lengthening of ocular axis will cause a series of fundus complications. Among them, high myopia macular disease is the main cause affecting visual function. Its pathological changes are closely related to the thickness and density of macular retina. Early structural examination can be carried out for early diagnosis and treatment [10].

Prospective Cross-Sectional Research Methods.
After admission, all patients underwent routine examinations, including vision, intraocular pressure, axial length, and slit lamp, and the basic data of all patients were counted and recorded by using a self-made patient basic data questionnaire, mainly including age, gender, contact information, home address, equivalent spherical mirror, and axial length [11]. All patients underwent OCTA test. The specific methods are 2 Scanning as follows: help patients take their seats and adjust their eyeballs to a reasonable position. The frequency domain system RTVue XR Avanti was purchased from an American company. Collect the microvessel density and retinal thickness in the macular region. The relevant scanning parameters are set as follows: the scanning frequency is 70 kHz, the light source is 840 nm, and the bandwidth is 45 nm. All patients are required to complete the examination scan of both eyes in the same examination [12]. The microvascular maps of the surface and deep layers of the retina were obtained by automatic stratification. The retinal thickness pattern was collected, and the scanning range was 5 mm × 5 mm, the retinal thickness in the central area of macula, above the inner ring, below the inner ring, nasal side of the inner ring, temporal side of the inner ring, and nasal side of the outer ring was calculated by automatic stratification. Outdoor activities can inhibit myopia by secreting dopamine. Wearing antiblue light glasses at night can improve sleep quality and reduce the incidence of myopia. Lutein eye patch can supplement various nutrients to protect photoreceptor cells to prevent vision decline. Atropine, photobiological goggles, and breastfeeding light instrument to thicken the choroid to improve myopia, and eye training to enhance the ability of the ciliary muscle to adjust, these methods are useful for myopia improvement. In the strategy of prevention and control of myopia, we should combine these methods to treat together, wear antiblue light glasses when facing the computer at work and apply lutein eye patch after get off work to supplement the nutrients consumed by the eyes, or photobiomodulation Repair damaged cells and thicken the choroid, participate in outdoor activities to stimulate dopamine secretion, etc., in order to maximize the deterioration of myopia, and to protect young children who have not developed high myopia more quickly. Figure 2 shows the average of children's ocular axis development, and Figure 3 shows the trend of myopia and high myopia in recent years and in the future. All patients were examined routinely, and their visual acuity, intraocular pressure, and optometry were checked. Then, the same OCTA (Cai Si OCT5000) examination was performed. The patient took the seat and adjusted the eyeball to a reasonable position. Then, the device frequency was set to 70 kHz, the wavelength was controlled at 840 mm, and then, the bandwidth was further set to 35 mm. The microvessel density pattern was controlled within 3 mm × 3 mm, scan the center of the concave sitting position in the form of a fence, scan both horizontally and vertically, and then remove the motion artifact. The time is controlled at about 2.9 s [13].

Statistical
Analysis. SPSS 20.0 software was used to analyze all the data. The equivalent sphericity and axial level of patients with different degrees of myopia were also different. It is considered that with the continuous increase of myopia, the ocular axis expands, and the retina of myopia without fundus disease has changed accordingly, resulting in obvious changes in the above indicators. High myopia is prone to retinal detachment, hydrops, floaters, etc., and even lead to permanent blindness. Supplementing enough lutein can make the eyes have enough nutrition, which can reduce the occurrence of lesions. Tests have shown that lutein can help patients with age-related macular degeneration to improve vision. Pos-sibly related to altered fluid transport in the social and development jump. There is a project phone of ions and water between the social and the retinal verse equipment. The study found that in the case of recovery of emmetropia after form deprivation myopia, with thickening of the choroid, there is an area of high osmotic pressure that is in the retina during form it, but moves to the outside after vision recovery. For the choroid, shifting the location of high osmotic pressure changes the flow of them, allowing fluid from the rest to flow to the choroid, thereby thickening the choroid. Studies have explored ways of choroidal thickening and found not just one, but as many as five. Choroidal thickening can improve myopia to a certain extent, that is to say, we can improve myopia in five ways from the choroidal thickening alone. And choroidal thickening is only one of the ways to improve myopia. Myopia is a multifactor eye disease, and there are many ways to improve it. In addition to the abovementioned choroidal thickening, outdoor activities secrete dopamine, sufficient sleep every night, and high-density macular pigment, etc. have also been found to have the effect of improving myopia. There are five ways of choroidal thickening. Studies have found that atropine, OK mirror, and myopia defocusing methods may  3 Scanning regulate choroidal thickening in different ways, but they can all make choroidal thickening. If we use the combination therapy method, when using atropine eye drops, and also use OK lens or myopia defocus treatment, the choroidal thickening will be greater, and the effect of myopia improvement will be more obvious. In addition, the levels of microvessel density in the surface and deep layers of macula in the three groups were gradually increased [14]. This suggests that myopia is closely related to the change of microvessel density in macula, that is, with the increasing degree of myopia, the microvessel density in macula also shows a corresponding change. The author believes that the increase of myopia degree will lead to more obvious extension of ocular axis, then promote the reduction of retinal thickness, further reduce oxygen demand and blood circulation, and finally change the microvessel density in macula. Therefore, the ocular axis and retinal thickness may be important factors leading to the change of microvessel density, which should be paid attention to [15]. Figure 4 shows the decline curve of children's hyperopia reserve age. The detection of vascular parameters in the macular region of myopia by OCTA is also gradually rising, but most studies know little about the peripheral vessels in the macular region, and few studies analyze the macular blood flow parameters separately. In this study, we used a high-resolution system to quantitatively compare the density of shallow and deep capillaries and retinal thickness in the macular region of adolescents and children with different diopters and explore their correlation with diopters, in order to find the thickness in myopia adolescents and children with different diopters, and provide more clinical evidence for myopia prevention and control [16]. Figure 5 shows the effect of ocular axis extension.

Basic Data Comparison Method.
A total of 115 adolescents and children were included. There was no significant difference in age and gender among the four groups (P > 0:05). The SE of the four groups were 0 ± 0:3, -1:7 ± 0:6, −4:2 ± 0:9 , and −7:7 ± 1:5D, respectively (P < 0:001). We believe that the lengthening of ocular axis may lead to the thinning of retina and the reduction of oxygen demand, resulting in the reduction of blood circulation and the decrease of vascular density. However, this study shows that with the increase of myopia, only the macular vascular density of ultrahigh myopia decreases significantly, which may be related to the small sample size of this study or the individual differences of the subjects [17]. For myopia, an eye disease with a high incidence and incurable, you may not know that it is also related to changes in choroidal thickness. The choroid is also involved in the refraction adjustment of the eyes. By increasing its own thickness, it pushes the position of the retina forward and shortens the distance between the focal plane and the retina, thereby improving the blurred image of myopia to a certain extent. Although no excellent prove in its thickness was seen in mild and moderate myopia, there was a significant difference in choroidal thickness between mild and high or very high myopia groups. The choroidal thickness was thinner in subjects with high myopia and thicker in those with low. This is consistent with previous knowledge that choroidal thickness was significantly negatively correlated with diopter. Choroidal thickening is an important indicator of myopia improvement, so it is necessary to explore the possible causes of changes in choroidal thickness. In this study, we also found that the retinal vascular density of fovea was not correlated with the equivalent spherical mirror and the length of ocular axis, while the parafoveal vascular density was positively correlated with things. We believe that the degree of myopia increases and the eyeball gradually extends, which causes the mechanical expansion and thinning of the retina, the straightening of retinal blood vessels and the narrowing of blood vessel diameter, resulting in the reduction of blood vessel density [18]. Figure 6 shows the prevalence of myopia at different ages. Because the fovea is closely connected with the vitreous, the influence of fovea on vascular density is small. It was found that there was no proof of difference in social vascular density in different degrees of myopia. Figure 7 shows the factors that reduce retinal vascular density. It may be related to the younger age and myopia of the subjects, and the fundus changes are mainly located in the peripheral retina. Therefore, the mechanism of the effect of different myopia diopters on macular vascular density needs to be further studied [19].

Results and Analysis
In the correlation analysis of macular vascular density, retinal thickness, and diopter in adolescents and children with different myopia diopters, this study found that in general, shallow capillary density, deep capillary density, and retinal thickness were negatively correlated with myopia diopter. That is, the detection values of these three indicators decrease with the increase of myopia diopter, which is consistent. It may be due to the increase of myopia diopter, the growth of ocular axis, and the stretching of retina, so that the diameter of blood vessels decreases and the density of blood vessels decreases [20]. Choroidal thickening may be associated with increased size and number of capillary openings. The capillaries of the choroid come down to Bruch's membrane, then to the retinal pigment epithelium, and then to the photoreceptor area. When the oxygen and nutrients of the capillaries and the fluid flow out through the orifices of the blood vessels, they will be screened and passed by the blood-retinal barrier formed by Bruch's membrane and the retinal pigment epithelium, and the fluid that cannot pass through the barrier will stay in the When the orifice is enlarged and the number of openings increases, it means that the fluid flow of the choroid will also increase, and the natural choroid will thicken. With the increase of myopia, the thickness of retina and choroid becomes thinner, while the thickness of nerve fiber layer decreases and the area of peripheral atrophy increases. To a certain extent, it can increase the risk of a series of pathological changes such as macular hemorrhage, retinal hole, retinal split, and retinal detachment, which will lead to visual loss and seriously threaten the physical and mental health of patients and their existing visual function. There were significant differences in the density of superficial capillaries in the whole macular region, inner ring, temporal side of inner ring, and nasal side (P = 0:033, 0:024, 0:018, 0:032), and there was no significant difference in other ranges (P > 0:05). The mechanism of this pathological change is not completely clear, but it is mainly closely related to the blood supply of retina and choroid. Figure 8 is a curve of the relationship between age and myopia incidence rate. As the sharpest part of vision on the retina, the macular fovea produces pathological changes, which will also lead to serious negative effects on vision [21]. Due to the limitation of cross-sectional study, the included sample size is relatively small, so it is difficult to rule out the impact of individual differences on the measurement results. It is urgent to further increase the sample size to further confirm the research results. In addition, children's eyeballs are in the period of development and growth, and the influence of age can not be ignored. Due to the limitation of sample size, there is no stratified study on age in this group. In conclusion, OCTA can be used as a noninvasive and practical imaging technology to quantitatively evaluate and find various early pathological changes related to ametropia. The discovery of these early changes provides key evidence for the prevention of early complications of the disease.

Conclusion
It should be noted that most of the previous research reports focus on the macular retinopathy of the elderly, while there are few studies on similar lesions in juvenile myopia, which is also the frontier and innovation of this study. From the results of this study, it can be seen that juvenile myopia may also affect the macular microvessel density and retinal thickness of patients. In the process of clinical diagnosis and treatment in the future, we should pay full attention to the ocular examination data of such patients, so as to prevent myopia and related complications more scientifically and objectively. With the gradual increase of myopia, a series of pathological changes will occur in the eyeball, such as the elongation of the ocular axis, the weakening of mechanical properties and the stretching and thinning of the sclera. The capillary density of the whole macular region, the inner ring and its temporal and nasal superficial layer is positively correlated with SE   5 Scanning macular region, the thickness of the macular region becomes significantly thinner. We found that there was a positive correlation between retinal vascular density and retinal thickness in the fovea and above of myopia. The application of OCTA in patients with different diopters can find that the changes of retinal vascular density and thickness in macular region are closely related to the diopter of clinical patients.

Data Availability
The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest
The authors declare that they have no conflicts of interest.